Device for accommodating receptacles and associated container

ABSTRACT

The invention relates to a device and a container for accommodating, filling, tempering, storing, emptying and transporting receptacles for biological, biochemical and biopharmaceutical substances, in particular liquids.

FIELD OF THE INVENTION

The invention relates to a device and a container for accommodating, filling, tempering, storing, emptying and transporting receptacles for biological, biochemical and biopharmaceutical substances, in particular liquids.

BACKGROUND OF THE INVENTION

Said substances are liquids such as protein solutions, protein mixtures, amino acid solutions, DNA solutions, nucleic acid solutions, blood plasma or similar, in particular.

Such substances and their packaging (receptacles) must be sterile as a rule. The substances are often conserved by freezing with a view to storage and/or transportation, for example. Frozen in receptacles, the substances are temporarily stored in cold stores or transported in the deep-frozen state before the substances are thawed in another method step and subjected to additional processing (treated). These methods steps are also conducted as a means of influencing the quality of the substances.

The substances are usually packaged in flexible plastic receptacles. This being the case, the process of filling and emptying them represents a technical problem, on the one hand as regards sterility and on the other hand as regards the mechanical strength of the receptacles.

The disadvantage of systems known from practical experience is that the receptacles are firstly filled, then placed in a refrigerated vessel and deep-frozen, before they are removed from the refrigerated vessel again following temporary storage or transportation and thawed. Accordingly, the sterility may be at risk. There is also a risk of damage to the receptacles, which would undesirably lead to leakage of the relevant substances.

SUMMARY OF THE INVENTION

The underlying objective of the invention is to propose an alternative option for packaging the receptacles. The intention is to optimise as many of the following processing and treatment steps as possible, compared with the prior art: accommodation of the receptacles, filling of the receptacles, tempering of the substances in the receptacles, storage of the filled receptacles, emptying of the receptacles.

The invention is based on the following considerations. The receptacles are placed in a holder device. This device contains several compartments and each compartment is used to accommodate one or more receptacles. Walls bounding the compartments are used to temper the receptacle contents. The receptacles are placed in the compartments through an appropriate opening. Having been placed in the compartments, in other words in the device, the receptacles can be filled and then tempered. For tempering purposes, for example for freezing a liquid in the container, the walls of the compartments are designed so that a fluid (heat-transfer medium) is able to circulate through at least parts of them.

Such a device with receptacles may be placed in a co-operating container which is used as a transport or storage container for the device and receptacles.

Another option is to place the device in the container first of all and then insert, fill and temper the receptacles, as explained.

The container has a tempered and/or isolated housing. The latter is intended to ensure that the requisite temperature level is maintained for as long as possible, even without active tempering, for example when the container is being transported. The container itself is opened or closed by means of a door or a cover. The door or cover may be of a design corresponding to the walls of the device. As a rule, however, it is sufficient for the lid (door, cover) to be thermally isolated and to be so such that isothermal conditions prevail in the interior as far as possible for a specific period of time, in other words in the region of the device, compartments and receptacles.

A heat-transfer medium (including coolant) is fed in and out via appropriate wall connectors (fittings). For example, a coolant is fed through the walls and transfers the temperature to the receptacles, preferably lying flat against the walls, and hence to the liquid in the receptacle. The tempering effect is more pronounced, the bigger the contact surface is between the wall/receptacle.

If the device is placed in the container empty, in other words insertion and tempering of the receptacles does not take place until in the container, the medium used for tempering purposes can be supplied from a unit disposed in or on the container or which can be connected to the container, for example a cooling unit. To this end, the co-operating connectors (fittings) may be run through a wall of the container and are preferably in turn thermally isolated.

Removal of the receptacles takes place in the reverse order from that in which they are inserted. The receptacles may be removed together with the tempered contents, in particular deep-frozen liquid, and subjected to further processing. However, a significant advantage of the solution proposed by the invention is the fact that thawing can also take place in the device/in the container for example. To speed up this process, a hot fluid may be circulated through the walls of the compartments, for example. The receptacles may also be emptied before being removed from the device, preferably via a bottom, outlet-side end, as will be explained in more detail below.

A major aspect of the invention is the fact that the construction is selected so that the thermal expansion which occurs during the process of freezing liquids is compensated. To this end, the compartments are designed so that they are variable or the walls bounding the compartments are able to move, i.e. their distance from one another increases as the container contents “grow”, thereby increasing the compartment volume.

In its most general embodiment, the invention relates to a device for accommodating and transporting receptacles for biological, biochemical and biopharmaceutical substances incorporating the following features:

-   -   several compartments disposed adjacent to one another for         accommodating at least one receptacle each,     -   every compartment is bounded by at least two walls extending         parallel at a distance apart from one another,     -   a fluid is able to circulate through at least parts of the         walls, which are provided with co-operating connectors for fluid         lines,     -   at least one wall of each compartment is displaceable in a         direction perpendicular to the walls,     -   at least one wall of the device is displaceable in a direction         perpendicular to the walls against the action of at least one         spring element.

The expression “spring element” within the meaning of the invention includes all types of construction elements suitable for returning the walls of the device to the original position, for example when the receptacle contents are thawed or removed. Accordingly, the purpose of the spring element is to compensate in situ for the displacement of the compartment walls due to thermal expansion of the receptacle contents.

In this respect, it is sufficient in principle to allow a single spring element to act on an external wall surface of the device. A similar embodiment with four spring elements will be described in more detail below as part of the description of the drawings. However, it is also possible to provide corresponding spring elements inside individual compartments, for example tension springs, which extend between co-operating walls of a compartment. As the receptacle contents expand, the distance of the walls can be made bigger because the walls are designed so that they can be displaced. A co-operating spring element would then expand and be placed under an initial tension. After thawing, the distance between the walls would become shorter again and the walls would automatically be returned to their original position due to the spring element.

In one embodiment, the walls are guided along rails extending in the direction perpendicular to the walls. The rails may be run through the walls, as explained below with reference to an example of an embodiment. Other ways of guiding and mounting the walls are also possible.

The spring element is usually secured to a bearing by means of a first portion. This maybe a frame of the device, for example. A second portion of the spring element is then loosely supported against a co-operating counter-bearing. This might be the external face of an external wall of the device, for example.

In the case of the embodiment with a tension spring mentioned as an example above, both end portions of the spring element would be secured to co-operating wall portions.

Examples of spring elements include components from the group comprising compression springs, tension springs, leaf springs, pneumatic springs, elastomer bodies, caoutchouc bodies, rubber bodies, hydraulic rams, pneumatic rams.

At least one wall may bound two adjacent compartments. This is rational because tempering of the wall simultaneously acts on two compartments/chambers.

Clearly, this does not apply to an external wall of the device.

In one embodiment of the invention designed to optimise packing of the receptacles in the compartments, every compartment is additionally bounded by at least two side faces which are disposed at a distance from one another and extend essentially perpendicular to the walls. This being the case, these side faces constitute vertical boundary surfaces for the compartments and run in the peripheral region of the walls accordingly. This results in a cuboid space for each compartment in particular, although other geometric shapes would be possible.

When the device is in its functional position, these side faces (side walls) maybe extended at their bottom end in order to format least a partial base surface for each compartment. This being the case, the angle may be such that the base surface subtends an angle of >90° with a co-operating side face.

As seen in side view, this corresponds to a sort of “funnel shape”, and a middle portion may be left free, which simultaneously services as an outlet opening for the receptacle and the liquid contained in it.

To enable the distance of adjacent walls of a compartment to be varied, the side faces must either be elastic or oversized, i.e. have a width which corresponds to at least the anticipated maximum distance of the walls.

In an alternative embodiment, the side faces are guided in grooves of the walls and these grooves have a depth which is bigger than an anticipated maximum displacement of oppositely lying walls of a compartment. As the wall distance becomes bigger, the side faces are then at least partially released from the grooves. They are returned to the grooves as soon as the walls move back towards one another again under the effect of the spring element. From a mathematical point of view, it is sufficient to design the grooves with a depth corresponding to half the maximum displacement of co-operating walls. However, since there is no way of guaranteeing that oppositely lying portions of the side faces will move uniformly out of the grooves or into the grooves, the proposed maximum depth represents a safety measure.

If the side faces are rigid, they should be made from a material with a low friction at least in the region of the surface, in order to facilitate displacement inside the grooves. A material with a base of polytetrafluoroethylene is suitable for this purpose, for example.

The dimensions of the device are such that bigger receptacles can also be accommodated, for example receptacles with a volume of significantly more than 10 litres, and volumes of >50 litres, >100 litres, >250 litres up to 1,000 litres and more are possible.

As a rule, it is sufficient to use an independent cooling unit for freezing and/or thawing the liquids in the receptacles. After the tempering operation, the cooling unit can be separated from the device/container so that the container can finally be taken to a cold store and/or transported. Providing a separate cooling unit means that the size of the container can be limited, which is particularly important for transportation purposes.

In one embodiment, an auxiliary unit for tempering the cavity enclosed by the housing is integrated in the container. This may be useful for long journeys during transportation when the isolating effect of the container is not enough to keep the temperature in the interior of the container constant, in other words in the region of the device/receptacles.

Such a tempering/cooling unit may have an electric connecting wire, which can be supplied during air transport by the on-board voltage of the aircraft, for example. It would also be possible to provide an electrical connection to the auxiliary tempering unit via a battery. This battery may also be integrated in the container. A generator may also be used to generate power.

Other features of the invention are defined in the dependent claims and other parts of the application. These include in particular the use of flexible disposable receptacles for the receptacles, which are designed so that they can be filled once they have been placed in the device and also emptied in the device. Emptying is made easier if the co-operating compartment base and/or a bottom portion of the co-operating receptacle is of an oblique design and the outlet opening of the receptacle lies at the lowermost end (in the functional position).

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be explained in more detail below with reference to different examples of embodiments. To this end, the drawings provide schematic diagrams as follows:

FIG. 1: is a perspective view of the device proposed by the invention;

FIG. 2: shows a structural detail illustrating how individual components of the device are guided and mounted;

FIG. 3: is a perspective view of a container with an integrated device of the type illustrated in FIG. 1;

FIG. 4: is a vertical section through the container illustrated in FIG. 3; and

FIG. 5: is a vertical section through the container illustrated in FIG. 3, offset by 90° compared with the diagram shown in FIG. 4.

The same reference numbers are used in the drawings to denote components that are the same or work in the same way.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENT

FIG. 1 illustrates a device comprising the following components.

Two outer walls 22.4, 22.5 and walls 22.1, 22.2, 22.3 disposed in between extending vertically parallel at a respective distance. A fluid line 23 runs from a connector region 23 z at a top portion of the co-operating wall in a meandering shape through each wall 22.1 . . . 22.5, to a connector region 23 a at the bottom region of each wall.

The walls 22.1 . . . 22.5 can be displaced, guided on rails 40.1, 40.2, 40.3, 40.4, disposed respectively in the corner region.

Disposed on the portion of the rails 40.1 . . . 40.4 extending beyond the wall 22.4 towards the rear (in the plane of the drawing) is a locking pin (not illustrated), so that the wall 22.4 is not able to slide down.

On the oppositely lying end (in other words at the front of the drawing), the rails 40.1 . . . 40.4 project beyond the (front) wall 22.5.

Each projecting portion of each rail 42, which is provided in the form of a round bar in each case, has a threaded portion at the free end with a nut 42.2 fitted on it, which forms a fixed bearing for a first end 42.1 of a compression spring 42, which lies with its other end 42.3 against the wall 22.5.

Formed between the walls 22.4, 22.1; 22.1, 22.2; 22.2, 22.3; 22.3, 22.5 are compartments 16.1, 16.2, 16.3, 16.4, which are laterally bounded (perpendicular to the wall faces) by side faces 44, 46 respectively, which sit loosely in grooves 48 of the walls 22.1 . . . 22.5. The side faces 44, 46 are made from polytetrafluoroethylene, a material which is dimensionally stable across a broad temperature range and generates a low surface friction when the co-operating side faces 44, 46 are moved along the grooves 48, as will be explained below. The side faces 44, 46 are inwardly angled (towards one another) at their bottom end in front of the rails 40.3, 40.4, and the respective angle α is approximately 100° respectively, so that portions 44 b, 46 b at the base end extend at an angle and in a funnel shape towards one another forming a base portion 44 o open at the middle.

The base portions 44 b, 46 b also extend in co-operating grooves 48 of the walls 22.1 . . . 22.5.

The described device is placed through a co-operating opening of an essentially cuboid-shaped container, as illustrated in FIG. 3. The container is opened/closed from above by means of a pivotably hinge-mounted cover 14.5. The cover 14.5 and wall and base regions 14.1, 14.2, 14.3, 14.4, 14.6, 14.7 of the container are thermally isolated. Ten openings 15 are provided in the wall region 14.1, which are fitted with inlet and outlet fittings 23 z, 23 a of the walls 22.1 . . . 22.5 and enable co-operating connections to fluid lines (not illustrated) to be established.

To this end, the device respectively the container is connected to a cooling unit (not illustrated), for example, which circulates an appropriate tempered heat-transfer medium through the walls 22.1 . . . 22.5.

Receptacles 24 are placed in the compartments 16.1 . . . 16.4 beforehand. The receptacles 24 are flexible plastic receptacles with a top filling device 24.2 and a bottom emptying device 24.1 in the region of the base opening 44 o.

Once filled, the receptacles 24 fill out the compartment volumes as far as possible in each case and a residual volume is usually left unused both in the receptacle 24 and in each compartment 16.1 . . . 16.4.

In order to freeze liquid substances with which the receptacles 24 have been filled, the walls 22.1 . . . 22.5 are then tempered. In the case of aqueous liquids, the volume of the substance increases due to the expansion in volume which occurs in water below 0° C. In order to compensate for this expansion, the device is provided with the displaceable walls 22.1 . . . 22.5 described above, which are now pushed along the rails 40.1 . . . 40.4 against the action of the springs 42.

In the reverse situation when the liquid substances in the receptacles 24 are thawing, the corresponding volumes are reduced again and the springs 42 ensure that the walls 22.1 . . . 22.5 are returned to their original position.

As the walls 22.1 . . . 22.5 are being displaced, the side faces 44, 46 are moved partially out of the grooves 48 and are then moved deep into the grooves 48 again.

FIG. 5 illustrates an auxiliary cooling unit 36, disposed in a chamber 34 of the container. The cooling unit 36 can be connected to the coolant lines running to the walls 22.1 . . . 22.5 to establish a flow connection. Its purpose is to ensure that the temperature in the container does not rise above or fall below critical values during longer periods of storage or longer journeys. This is important in the case of so-called cryoconservation of liquids, for example.

FIG. 5 also illustrates feet 32 of the container underneath the base 14.7.

Within the scope of the invention, the number of compartments and/or walls may be varied, several receptacles maybe disposed in one compartment, rigid instead of flexible receptacles may be used, inlet and outlet openings of the receptacles may be of a different design, different heat-transfer media may be used, the receptacle contents may be heated and/or cooled, different spring elements and/or a different number of spring elements may be used or the side walls may be made from a flexible material.

In the latter case, the width (in the longitudinal direction of the rails) of the side walls is selected so that it is at least as wide as the anticipated maximum distance of co-operating walls. The walls can then be fixedly joined to the side faces. In the normal situation, for example when filling the receptacles, the side faces then fold slightly open; however, they continue to provide a guiding action for the receptacles placed in the compartments. 

1. Device for accommodating and transporting receptacles for biological, biochemical and biopharmaceutical substances, comprising the following features: 1.1 several compartments disposed adjacent to one another for accommodating at least one receptacle each, 1.2 each compartment is bounded by at least two walls extending parallel at a distance from one another, 1.3 a fluid is able to circulate through at least parts of the walls which have co-operating connectors for fluid lines, 1.4 at least one wall of each compartment can be displaced in a direction perpendicular to the walls, 1.5 at least one wall of the device can be displaced in a direction perpendicular to the walls against the action of at least one spring element.
 2. Device as claimed in claim 1, in which the walls are guided along rails which extend in the direction perpendicular to the walls.
 3. Device as claimed in claim 1 in which the at least one spring element is secured to a bearing by a first portion.
 4. Device as claimed in claim 1, in which the at least one spring element is loosely supported against a co-operating counter-bearing by a second portion.
 5. Device as claimed in claim 1, in which the spring element is a component selected from the group comprising compression springs, tension springs, leaf springs, pneumatic springs, elastomer bodies, caoutchouc bodies, rubber bodies, hydraulic rams, pneumatic rams.
 6. Device as claimed in claim 1, in which at least one wall bounds two adjacent compartments.
 7. Device as claimed in claim 1, in which every compartment is additionally bounded by at least two side faces which extend at a distance apart from one another and essentially perpendicular to the walls.
 8. Device as claimed in claim 7, the side faces of which form vertical boundary faces for the compartments and extend in the peripheral region of the walls.
 9. Device as claimed in claim 7, in which the co-operating side faces of at least one compartment are angled towards one another at their bottom end when the device is in a functional position, forming an at least partial base surface.
 10. Device as claimed in claim 7, in which the base surface at least partially subtends an angle of more than 90 degrees with a co-operating side face.
 11. Device as claimed in claim 7, in which the side faces are guided in grooves of the walls.
 12. Device as claimed in claim 11, in which the grooves in the extension of co-operating side faces have a depth which is bigger than an anticipated maximum displacement of co-operating walls of a compartment relative to one another.
 13. Container with a thermally isolated housing which has at least one door or a cover and encloses a cavity for accommodating a device as claimed in claim
 1. 14. Container as claimed in claim 13, with at least a wall-side housing opening for accommodating at least one fluid-circulating line to the connector to at least one fluid line of at least one wall of the device.
 15. Container as claimed in claim 13, with an integrated auxiliary unit for tempering the cavity enclosed by the housing. 